PracticeUpdate Conference Series: IID 2018

BLZ-100 (Tozuleristide) Shown to Discriminate Between Subtle Molecular Subtypes of Basal Cell Carcinoma The first in-human study of BLZ-100 (tozuleristide), which selectively detects malignant tissue to enable more complete and precise surgical resection, has shown that the compound can discriminate between subtle molecular subtypes of basal cell carcinoma. M iko Yamada, PhD, of the University of Queensland in Brisbane, Australia, explained that skin as more precise and complete surgical removal of cancer. Surrounding normal tissue is spared. In this first in-human study, BLZ 100 was administered intravenously to 21 adult patients 2 days prior to excision of known/ suspected skin cancers.

cancer is often curable with complete excision. Wide margins are needed, how- ever, particularly for cancers on the face. BLZ-100 (tozuleristide) is an intraoperative fluorescent imaging agent (tumor paint) that selectively detects malignant tissue to enable more complete and precise surgical resection. Surgery is first-line therapy for most solid tumor cancers. Tumor paint products intend to improve cancer surgery by providing real-time, high-resolution visual- ization of cancer cells throughout surgery. The ability to see cancer cells in real time and high resolution throughout surgery should enable better detection as well

The first tumor paint product candidate, BLZ-100, is in phase I clinical trials for brain and breast cancers. Additional potential applications of BLZ-100 include prostate, lung, colorectal, and other solid tumor cancers. BLZ-100 is administered by IV injection, circulates within the body, and “light ups” cancer cells. It consists of an Optide, which binds and internalizes into cancer cells, and a fluorescent dye, which emits light in the near-infrared range. Preclinical utility of BLZ-100 was demon- strated in a wide range of cancer types, including brain, breast, prostate, lung, colorectal, skin, and sarcomas.

Doses were 1, 3, 6, 12, and 18 mg, with 3 to 6 patients per cohort. Fluorescence imaging was conducted before and up to 48 h after dosing. BLZ-100 was tolerated well. No serious adverse effects were observed. For intermediate dose levels (3–12 mg), 9 of 10 malignant lesions were considered positive for BLZ-100 fluorescence. This positivity led Dr. Yamada and col- leagues to explore differential gene expression profiles in basal cell carci- noma tumors, the most homogeneous of the examined lesions.

SecukinumabReduces CD4-Positive Th17, AsWell As CD8- andCD4-Positive Treg Cells inPatientsWith Plaque Psoriasis

In SCULPTURE, Psoriasis Area and Severity Index 75 responders at week 12 were randomized to double-blind main- tenance treatment of 300 or 150 mg of secukinumab, given in either a 4-week fixed-interval regimen or in a retreatment- as-needed regimen. Patients who completed 52 weeks of the SCULPTURE study were eligible to continue the same dose and regimen in the extension study (n=642). The primary objective of the extension study was to assess the long-term safety and tolerability of secukinumab in patients with moderate to severe plaque psoriasis. Efficacy measures included proportion of patients achieving Psoriasis Area and Severity Index 75/90/100.

Secukinumab has been found to reduce not only CD4-positive Th17, but also CD8- and CD4-positive T-regulatory (Treg) cells in patients with plaque psoriasis. This finding of a flow cytometry study to characterize changes in immune cell populations in psoriatic lesions treated with secukinumab was reported at IID 2018. E ric J. Yang, MD, of the University of California in San Francisco, explained that psoriasis is a chronic inflamma- demonstrated broad changes that occurred in lesioned skin.

Secukinumab, approved for plaque pso- riasis in 2015, is a recombinant human monoclonal IgG1/κ antibody that binds specifically to interleukin 17A. In 2017, 5-year data were reported on secukinumab for moderate to severe plaque psoriasis. The 5-year extension study was a multicenter, double-blind, open-label, 5-year extension to the core phase 3 SCULPTURE study.

tory skin disease that involves widespread immune dysregulation. Cell populations implicated in psoriasis include kerati- nocytes, dendritic cells, and Th17 cells. These produce excess tumor necrosis factor α, and interleukins 17 and 23. Studies evaluating the impact of biolog- ics on the molecular profile of psoriasis have used bulk skin tissue and have

14 PRACTICEUPDATE CONFERENCE SERIES • IID 2018